Crystal structure of anabolic steroid metabolite 4-chloro­androst-4-ene-3,17-dione

A metabolite of an anabolic steroid norchloro­testosterone acetate (NClTA) was successfully synthesized and characterized by ¹H NMR and ¹³C NMR spectroscopy and single-crystal X-ray diffraction. The position of the chlorine substituent and the absolute configuration of the mol­ecule were established.

Key indicators

Structure: I

• Single-crystal X-ray study
• T = 100 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.024
• wR factor = 0.065
• Data-to-parameter ratio = 15.2

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT911_ALERT_3_C Missing FCF Refl Between Thmin & STh/L=    0.600         15 Report
PLAT987_ALERT_1_C The Flack x is >> 0 -  Do a BASF/TWIN Refinement     Please Check

Alert level G
PLAT033_ALERT_4_G Flack x Value Deviates > 3.0 * sigma from Zero .      0.029 Note
PLAT480_ALERT_4_G Long H...A H-Bond Reported H4       ..CL1      .       2.88 Ang.
PLAT791_ALERT_4_G Model has Chirality at C4          (Sohnke SpGr)          R Verify
PLAT791_ALERT_4_G Model has Chirality at C5          (Sohnke SpGr)          S Verify
PLAT791_ALERT_4_G Model has Chirality at C8          (Sohnke SpGr)          S Verify
PLAT791_ALERT_4_G Model has Chirality at C12         (Sohnke SpGr)          S Verify
PLAT791_ALERT_4_G Model has Chirality at C13         (Sohnke SpGr)          R Verify
PLAT912_ALERT_4_G Missing # of FCF Reflections Above STh/L=  0.600          1 Note
PLAT913_ALERT_3_G Missing # of Very Strong Reflections in FCF ....          1 Note
PLAT978_ALERT_2_G Number C-C Bonds with Positive Residual Density.         19 Info

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   2 ALERT level C = Check. Ensure it is not caused by an omission or oversight
  10 ALERT level G = General information/check it is not something unexpected

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   8 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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Computing details

Data collection: APEX3 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015); program(s) used to refine structure: SHELXL (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

4-Chloroandrost-4-ene-3,17-dione

Crystal data

C18H23ClO2	Dx = 1.308 Mg m^−3
Mr = 306.81	Cu Kα radiation, λ = 1.54178 Å
Orthorhombic, P212121	Cell parameters from 9974 reflections
a = 7.4379 (4) Å	θ = 4.4–70.2°
b = 12.7142 (6) Å	µ = 2.18 mm^−1
c = 16.4790 (8) Å	T = 100 K
V = 1558.37 (13) Å^3	Block, clear light colourless
Z = 4	0.05 × 0.01 × 0.01 mm
F(000) = 656

Data collection

BRUKER D8 VENTURE diffractometer	2907 independent reflections
Radiation source: X-ray tube, Micro focus tube	2787 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.031
Detector resolution: 10.4167 pixels mm^-1	θmax = 70.1°, θmin = 4.4°
ω and φ scans	h = −9→9
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	k = −15→15
Tmin = 0.678, Tmax = 0.753	l = −20→19
18469 measured reflections

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.024	w = 1/[σ^2(Fo^2) + (0.0383P)^2 + 0.2052P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.065	(Δ/σ)max = 0.001
S = 1.04	Δρmax = 0.17 e Å^−3
2907 reflections	Δρmin = −0.18 e Å^−3
191 parameters	Absolute structure: Flack x determined using 1150 quotients [(I^+)-(I^-)]/[(I^+)+(I^-)] (Parsons et al., 2013)
0 restraints	Absolute structure parameter: 0.029 (4)
Primary atom site location: dual

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
Cl1	0.53413 (6)	−0.00451 (3)	0.67248 (3)	0.02851 (13)
O1	0.1878 (2)	−0.02569 (11)	0.74872 (9)	0.0345 (3)
O2	0.3004 (2)	0.70098 (13)	0.43229 (10)	0.0401 (4)
C1	0.2157 (3)	0.06557 (15)	0.73085 (11)	0.0242 (4)
C5	0.2976 (2)	0.36358 (14)	0.60909 (11)	0.0191 (3)
H5	0.259997	0.323792	0.559582	0.023*
C6	0.1640 (2)	0.45474 (14)	0.62010 (12)	0.0228 (4)
H6A	0.188454	0.489661	0.672646	0.027*
H6B	0.040622	0.425670	0.622443	0.027*
C17	0.3824 (2)	0.09845 (14)	0.68886 (11)	0.0214 (4)
C3	0.0974 (2)	0.24336 (14)	0.69275 (11)	0.0234 (4)
H3A	0.017607	0.300838	0.711313	0.028*
H3B	0.051866	0.217948	0.639818	0.028*
C7	0.1726 (2)	0.53763 (15)	0.55206 (12)	0.0243 (4)
H7A	0.128879	0.506525	0.500636	0.029*
H7B	0.093792	0.597774	0.565909	0.029*
C4	0.2882 (2)	0.28617 (13)	0.68182 (11)	0.0193 (3)
H4	0.319484	0.326567	0.731938	0.023*
C16	0.4260 (2)	0.19893 (13)	0.67251 (11)	0.0206 (3)
C13	0.4912 (2)	0.40302 (14)	0.59430 (11)	0.0197 (4)
H13	0.534533	0.439779	0.644250	0.024*
C9	0.4042 (3)	0.64247 (15)	0.46663 (12)	0.0278 (4)
C15	0.6121 (3)	0.23322 (15)	0.64898 (13)	0.0277 (4)
H15A	0.684117	0.170390	0.634705	0.033*
H15B	0.670068	0.267385	0.696210	0.033*
C2	0.0914 (3)	0.15384 (15)	0.75394 (12)	0.0263 (4)
H2A	0.125680	0.180934	0.808097	0.032*
H2B	−0.033061	0.126618	0.757601	0.032*
C8	0.3650 (2)	0.57594 (14)	0.54125 (11)	0.0215 (4)
C18	0.4268 (3)	0.64214 (15)	0.61467 (12)	0.0255 (4)
H18A	0.340763	0.699209	0.624110	0.038*
H18B	0.545813	0.671945	0.603545	0.038*
H18C	0.433172	0.597296	0.662951	0.038*
C14	0.6134 (2)	0.30946 (15)	0.57747 (12)	0.0262 (4)
H14A	0.737587	0.334569	0.567856	0.031*
H14B	0.572060	0.272622	0.527940	0.031*
C12	0.4880 (2)	0.48125 (14)	0.52440 (11)	0.0221 (4)
H12	0.435207	0.443399	0.476847	0.027*
C10	0.5982 (3)	0.62344 (17)	0.44187 (13)	0.0336 (5)
H10A	0.671889	0.687004	0.451795	0.040*
H10B	0.605681	0.605168	0.383565	0.040*
C11	0.6645 (3)	0.53098 (16)	0.49478 (13)	0.0302 (4)
H11A	0.735925	0.480383	0.462438	0.036*
H11B	0.738045	0.556310	0.540879	0.036*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0383 (2)	0.0235 (2)	0.0237 (2)	0.00946 (18)	0.00264 (17)	0.00324 (19)
O1	0.0444 (8)	0.0246 (7)	0.0345 (8)	−0.0055 (6)	0.0073 (7)	0.0060 (6)
O2	0.0503 (9)	0.0395 (8)	0.0305 (8)	0.0078 (8)	0.0007 (7)	0.0141 (7)
C1	0.0307 (9)	0.0246 (9)	0.0173 (9)	−0.0043 (8)	−0.0020 (7)	−0.0001 (7)
C5	0.0164 (8)	0.0212 (8)	0.0198 (8)	−0.0009 (7)	0.0004 (7)	−0.0029 (7)
C6	0.0190 (8)	0.0252 (9)	0.0241 (10)	0.0023 (7)	0.0021 (7)	0.0019 (7)
C17	0.0263 (9)	0.0229 (8)	0.0151 (8)	0.0034 (7)	−0.0013 (7)	−0.0013 (7)
C3	0.0189 (8)	0.0237 (9)	0.0275 (10)	−0.0015 (7)	0.0027 (7)	−0.0004 (7)
C7	0.0212 (8)	0.0279 (9)	0.0237 (9)	0.0042 (7)	−0.0011 (7)	0.0033 (7)
C4	0.0176 (7)	0.0199 (8)	0.0203 (8)	−0.0011 (6)	0.0008 (7)	−0.0025 (7)
C16	0.0206 (8)	0.0229 (8)	0.0183 (8)	0.0011 (6)	−0.0004 (7)	−0.0018 (7)
C13	0.0171 (8)	0.0208 (8)	0.0212 (9)	−0.0008 (7)	0.0026 (6)	−0.0022 (7)
C9	0.0387 (10)	0.0246 (9)	0.0202 (9)	−0.0019 (8)	0.0012 (8)	−0.0007 (8)
C15	0.0186 (8)	0.0259 (9)	0.0386 (11)	0.0029 (7)	0.0001 (8)	0.0025 (8)
C2	0.0260 (9)	0.0277 (9)	0.0253 (9)	−0.0046 (7)	0.0060 (7)	0.0006 (8)
C8	0.0241 (9)	0.0224 (8)	0.0179 (8)	0.0016 (7)	0.0004 (7)	0.0008 (7)
C18	0.0320 (10)	0.0232 (9)	0.0211 (9)	0.0018 (7)	−0.0011 (7)	0.0001 (7)
C14	0.0192 (8)	0.0261 (9)	0.0332 (10)	0.0025 (7)	0.0069 (8)	−0.0001 (8)
C12	0.0214 (8)	0.0242 (9)	0.0207 (9)	−0.0007 (7)	0.0031 (6)	−0.0026 (7)
C10	0.0411 (11)	0.0313 (11)	0.0285 (10)	−0.0027 (9)	0.0117 (9)	0.0048 (8)
C11	0.0281 (9)	0.0302 (10)	0.0323 (11)	−0.0007 (8)	0.0109 (8)	0.0021 (8)

Geometric parameters (Å, º)

Cl1—C17	1.7493 (17)	C13—C14	1.523 (2)
O1—C1	1.215 (2)	C13—C12	1.522 (3)
O2—C9	1.212 (3)	C9—C8	1.521 (3)
C1—C17	1.480 (3)	C9—C10	1.519 (3)
C1—C2	1.503 (3)	C15—H15A	0.9900
C5—H5	1.0000	C15—H15B	0.9900
C5—C6	1.538 (2)	C15—C14	1.526 (3)
C5—C4	1.552 (2)	C2—H2A	0.9900
C5—C13	1.544 (2)	C2—H2B	0.9900
C6—H6A	0.9900	C8—C18	1.544 (3)
C6—H6B	0.9900	C8—C12	1.538 (2)
C6—C7	1.540 (3)	C18—H18A	0.9800
C17—C16	1.345 (2)	C18—H18B	0.9800
C3—H3A	0.9900	C18—H18C	0.9800
C3—H3B	0.9900	C14—H14A	0.9900
C3—C4	1.530 (2)	C14—H14B	0.9900
C3—C2	1.521 (3)	C12—H12	1.0000
C7—H7A	0.9900	C12—C11	1.537 (2)
C7—H7B	0.9900	C10—H10A	0.9900
C7—C8	1.522 (3)	C10—H10B	0.9900
C4—H4	1.0000	C10—C11	1.544 (3)
C4—C16	1.518 (2)	C11—H11A	0.9900
C16—C15	1.502 (3)	C11—H11B	0.9900
C13—H13	1.0000
O1—C1—C17	121.74 (18)	C16—C15—H15A	109.0
O1—C1—C2	123.14 (18)	C16—C15—H15B	109.0
C17—C1—C2	115.01 (15)	C16—C15—C14	112.91 (15)
C6—C5—H5	107.2	H15A—C15—H15B	107.8
C6—C5—C4	110.95 (14)	C14—C15—H15A	109.0
C6—C5—C13	112.12 (14)	C14—C15—H15B	109.0
C4—C5—H5	107.2	C1—C2—C3	111.88 (15)
C13—C5—H5	107.2	C1—C2—H2A	109.2
C13—C5—C4	111.73 (14)	C1—C2—H2B	109.2
C5—C6—H6A	108.8	C3—C2—H2A	109.2
C5—C6—H6B	108.8	C3—C2—H2B	109.2
C5—C6—C7	113.78 (15)	H2A—C2—H2B	107.9
H6A—C6—H6B	107.7	C7—C8—C18	111.28 (15)
C7—C6—H6A	108.8	C7—C8—C12	109.28 (15)
C7—C6—H6B	108.8	C9—C8—C7	116.95 (16)
C1—C17—Cl1	113.65 (13)	C9—C8—C18	105.85 (15)
C16—C17—Cl1	121.62 (14)	C9—C8—C12	100.08 (14)
C16—C17—C1	124.31 (16)	C12—C8—C18	113.01 (15)
H3A—C3—H3B	107.9	C8—C18—H18A	109.5
C4—C3—H3A	109.3	C8—C18—H18B	109.5
C4—C3—H3B	109.3	C8—C18—H18C	109.5
C2—C3—H3A	109.3	H18A—C18—H18B	109.5
C2—C3—H3B	109.3	H18A—C18—H18C	109.5
C2—C3—C4	111.81 (15)	H18B—C18—H18C	109.5
C6—C7—H7A	109.6	C13—C14—C15	110.60 (15)
C6—C7—H7B	109.6	C13—C14—H14A	109.5
H7A—C7—H7B	108.2	C13—C14—H14B	109.5
C8—C7—C6	110.07 (15)	C15—C14—H14A	109.5
C8—C7—H7A	109.6	C15—C14—H14B	109.5
C8—C7—H7B	109.6	H14A—C14—H14B	108.1
C5—C4—H4	107.5	C13—C12—C8	112.60 (14)
C3—C4—C5	111.00 (14)	C13—C12—H12	106.5
C3—C4—H4	107.5	C13—C12—C11	119.74 (15)
C16—C4—C5	110.76 (14)	C8—C12—H12	106.5
C16—C4—C3	112.21 (14)	C11—C12—C8	104.11 (14)
C16—C4—H4	107.5	C11—C12—H12	106.5
C17—C16—C4	120.72 (15)	C9—C10—H10A	110.6
C17—C16—C15	123.32 (16)	C9—C10—H10B	110.6
C15—C16—C4	115.87 (14)	C9—C10—C11	105.83 (16)
C5—C13—H13	108.8	H10A—C10—H10B	108.7
C14—C13—C5	109.38 (14)	C11—C10—H10A	110.6
C14—C13—H13	108.8	C11—C10—H10B	110.6
C12—C13—C5	108.50 (14)	C12—C11—C10	102.70 (16)
C12—C13—H13	108.8	C12—C11—H11A	111.2
C12—C13—C14	112.45 (15)	C12—C11—H11B	111.2
O2—C9—C8	126.60 (18)	C10—C11—H11A	111.2
O2—C9—C10	125.27 (19)	C10—C11—H11B	111.2
C10—C9—C8	108.13 (16)	H11A—C11—H11B	109.1
Cl1—C17—C16—C4	175.86 (13)	C7—C8—C12—C11	166.87 (15)
Cl1—C17—C16—C15	−7.7 (3)	C4—C5—C6—C7	177.20 (14)
O1—C1—C17—Cl1	−2.6 (2)	C4—C5—C13—C14	59.07 (19)
O1—C1—C17—C16	−175.31 (19)	C4—C5—C13—C12	−177.92 (14)
O1—C1—C2—C3	−150.53 (19)	C4—C3—C2—C1	−56.7 (2)
O2—C9—C8—C7	30.3 (3)	C4—C16—C15—C14	−48.3 (2)
O2—C9—C8—C18	−94.3 (2)	C16—C15—C14—C13	53.9 (2)
O2—C9—C8—C12	148.1 (2)	C13—C5—C6—C7	51.5 (2)
O2—C9—C10—C11	−171.2 (2)	C13—C5—C4—C3	−176.96 (14)
C1—C17—C16—C4	−12.0 (3)	C13—C5—C4—C16	−51.60 (19)
C1—C17—C16—C15	164.43 (18)	C13—C12—C11—C10	−165.63 (16)
C5—C6—C7—C8	−52.9 (2)	C9—C8—C12—C13	174.71 (15)
C5—C4—C16—C17	−136.86 (17)	C9—C8—C12—C11	43.51 (18)
C5—C4—C16—C15	46.5 (2)	C9—C10—C11—C12	18.2 (2)
C5—C13—C14—C15	−59.3 (2)	C2—C1—C17—Cl1	173.68 (13)
C5—C13—C12—C8	58.98 (19)	C2—C1—C17—C16	1.0 (3)
C5—C13—C12—C11	−178.21 (16)	C2—C3—C4—C5	170.25 (14)
C6—C5—C4—C3	57.13 (18)	C2—C3—C4—C16	45.7 (2)
C6—C5—C4—C16	−177.52 (14)	C8—C9—C10—C11	8.9 (2)
C6—C5—C13—C14	−175.66 (15)	C8—C12—C11—C10	−38.77 (19)
C6—C5—C13—C12	−52.7 (2)	C18—C8—C12—C13	62.56 (19)
C6—C7—C8—C9	168.92 (15)	C18—C8—C12—C11	−68.63 (19)
C6—C7—C8—C18	−69.28 (19)	C14—C13—C12—C8	−179.90 (15)
C6—C7—C8—C12	56.2 (2)	C14—C13—C12—C11	−57.1 (2)
C17—C1—C2—C3	33.2 (2)	C12—C13—C14—C15	−179.92 (15)
C17—C16—C15—C14	135.14 (19)	C10—C9—C8—C7	−149.86 (17)
C3—C4—C16—C17	−12.2 (2)	C10—C9—C8—C18	85.56 (18)
C3—C4—C16—C15	171.12 (16)	C10—C9—C8—C12	−32.04 (19)
C7—C8—C12—C13	−61.93 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2A···O2^i	0.99	2.60	3.563 (2)	165
C10—H10A···O2^ii	0.99	2.57	3.398 (3)	141
C18—H18B···O2^ii	0.98	2.56	3.507 (3)	163
C10—H10B···O1^iii	0.99	2.48	3.443 (3)	164
C4—H4···Cl1^iv	1.00	2.88	3.8202 (18)	158

Symmetry codes: (i) −x+1/2, −y+1, z+1/2; (ii) x+1/2, −y+3/2, −z+1; (iii) x+1/2, −y+1/2, −z+1; (iv) −x+1, y+1/2, −z+3/2.